In primary cervical cancer screening, the follow up after a positive test for high-risk Human Papilloma Virus (hrHPV) is fairly well established, whereas this is not the case for women who do not attend primary screening and alternatively are offered screening by self-sampling. Looking at ≥CIN2 cases, we here compare the distribution of hrHPV genotypes in under-screened women who were screened through HPV self-sampling (Copenhagen Self Sampling Initiative, CSi, preliminary date) to that of women attending primary screening (The Danish Horizon study). Based on genotype, could some of these women benefit from direct referrals to colposcopy rather than referral to follow up cytology?
From both studies, we included women aged ≥30 years (Horizon: N=2974, CSi: N=4440). Women with a positive hrHPV test at baseline (Horizon N=461, CSi N=462) and a subsequent histological diagnosis of ≥CIN2 were compared by retrieving genotype result from the baseline sample. The follow up periods for Horizon is 3 years at present, while follow up currently is up to 12 months for CSi. All HPV DNA testing was undertaken using the CLART HPV2 assay (Genomica, Spain). ≥CIN2 cases were identified through passive follow-up in the Danish Pathology Data Bank.
Fifty ≥CIN2 cases were identified among primary screened women, corresponding to 10.8% of hrHPV positive women in the group. Among those offered HPV self-sampling 58 ≥CIN2 cases were detected, equal to 12.6% of hrHPV positive cases. The mean ages of the women included in the analysis were 39 (±10.5) and 44 (±10.6) years, for Horizon and CSi respectively. One-third of the under-screened CSi women were above the age of 50, with only 10% being above the age of 50 among the Horizon women. HPV16 was the most frequent genotype observed in the baseline sample with 23% (Horizon) and 34% (CSi). HPV52 and HPV31 were the 2nd and 3rd most prevalent genotypes. For under-screened women offered self-sampling, HPV16, 52 and 31 accounted for 56% of all observed ≥CIN2. The frequency of the remaining 10 hrHPV genotypes differed considerably between the two groups.
Although based on small numbers, HPV16, HPV52 and HPV31 were the most prevalent genotypes in both groups. Primary screened women with ≥CIN2 were younger compared to under-screened women offered self-sampling, however this is an effect of women not participating in primary screening on average being older. The high frequency of HPV16, HPV52 and HPV31 leading to ≥CIN2, and the womens status as under-screened lead us to propose that under-screened women accepting self-sampling and found positive for any of these genotypes should be directly referred for gynaecology examination and colposcopy.